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Induction of Experimental Autoimmune Hypophysitis in SJL Mice
Published on: December 18, 2010
Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans
G Mastorakos1, G P Chrousos, J S Weber
1Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
The Journal of Clinical Endocrinology and Metabolism
|December 1, 1993
Summary
Interleukin-6 (IL-6) effectively stimulates the hypothalamic-pituitary-adrenal (HPA) axis in cancer patients, showing modest toxicity. This cytokine may serve as a viable alternative for HPA axis testing compared to other methods.
Area of Science:
- Endocrinology
- Immunology
- Oncology
Background:
- Inflammatory cytokines like tumor necrosis factor-alpha, IL-1, and IL-6 activate the hypothalamic-pituitary-adrenal (HPA) axis.
- Previous studies on TNF-alpha and IL-1 were limited by severe toxicity, such as hypotension.
- IL-6 has shown only modest toxicity in animal studies.
Purpose of the Study:
- To evaluate the HPA axis-stimulating ability of recombinant IL-6 in cancer patients.
- To assess the safety and efficacy of IL-6 for HPA axis testing in a clinical setting.
Main Methods:
- A phase I trial involving cancer patients with good performance status.
- Daily subcutaneous injections of 30 micrograms/kg IL-6 for seven consecutive days.
- Measurement of plasma ACTH and cortisol levels to assess HPA axis response.
Main Results:
- IL-6 induced significant and prolonged elevations in plasma ACTH and cortisol on day one.
- Blunted ACTH responses were observed on day seven, potentially due to elevated baseline cortisol.
- The overall cortisol response magnitude remained similar on day seven, indicating adaptation.
Conclusions:
- Chronic IL-6 administration leads to a new equilibrium in HPA axis feedback regulation.
- IL-6 demonstrated modest toxicity, suggesting its potential utility for HPA axis clinical testing.
- IL-6 offers a potentially safer alternative to the insulin tolerance test for evaluating HPA axis function.
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